Lead is a well-known toxic element. Its presence in the human body has serious negative consequences on the human health and development even in trace concentrations. Developmental health problems in children exposed to lead such as reduced cognitive abilities, impaired hearing, hyperactivity and delayed puberty are particularly concerning. According to the Environmental Protection Agency (EPA) in 2010 an estimated 535,000 children had a blood level of 5 ?g/dL and about 24 million homes in the United States still had significant lead-based paint hazards. Blood lead levels were also reported to be higher for children ages 1-5 years old from lower-income families and for certain racial and ethnic groups. Lead accumulates predominantly in the bone tissue following prolonged exposure. Therefore, in vivo x-ray fluorescence (XRF) measurements of lead concentration in bone is an important assessment tool for human lead burden. These measurements are currently performed using an analytical method based on the detection of K-shell XRF photons of lead (KXRF) in the tibia bone using a 109Cd radioactive source. Due to the relatively high costs and radiation safety concerns surrounding radioactive sources, the KXRF method usage was limited to several laboratories worldwide. The development of a novel, inexpensive, portable, and easy-to-use method for bone lead measurements has the potential to assess on a large scale the lead exposure of children. An alternative investigated in the past was to use the lower photon energy L-shell XRF detection of lead in bone (LXRF). Unfortunately, the LXRF studies reported sensitivity and accuracy values which did not meet the requirements of in vivo human lead bone measurements. Significant improvements to the past LXRF method can be made by using a confocal x-ray fluorescence (C-XRF) technique. The C-XRF is a novel approach to the traditional XRF that, in addition to the x-ray source and detector, uses two polycapillary x-ray lenses (PXLs): one focuses the excitation beam on a small volume element (SVE) within the sample (~1 nL) while the other guides the emergent XRF photons from the same SVE onto the x-ray detector. The advantages of the C-XRF technique are: 1. Better minimum detection limit (MDL) of lead due to x-ray scatter reduction associated with the PXLs collimation of the incident and emergent x-ray beams, 2. Well-defined incident-emergent x-ray beam geometry supports an integrated spectrometric calibration procedure eliminating the need of separate soft tissue measurements, 3. Improved tradeoff between the radiation dose and lead MDL which is possible by the significantly reduced human tissue volume irradiated in the C-XRF technique. A systematic study of lead C-XRF measurements in human tibia bone phantoms with overlying soft tissue is proposed. The results can lead to the design of a portable easy-to-use C-XRF device which can significantly elevate the role of in vivo bone lead measurement as a research, diagnostic, and screening tool.